This research proposal examines the role of suppressor cells in melanoma patients. These studies are based on the working hypothesis that increased suppressor cell activity is an important immunoregulatory abnormality in melanoma. Preliminary evidence is presented that demonstrates increased suppressor activity in three consecutively studied melanoma patients, including one with a very early stage of disease. We will use specific immunologic reagents that recognize cell surface markers uniquely expressed on subpopulations of normal human T lymphocytes. The fluorescent activated cell sorter and rosetting techniques can then be used to identify those subsets with suppressor activity. Experiments will be performed to partially characterize mechanisms of suppressor function. This information will be used to examine for abnormalities of suppressor activity in melanoma patients. In addition, we would examine whether other factors such as immune complexes and histocompatability antigens may be associated with activation of suppressor cells and thereby influence the course of disease. By serial examination, suppressor cell activity would be monitored in melanoma patients undergoing combinations of surgery, immunotherapy and chemotherapy. Serial determinations of suppressor cell activity will be determined in carefully matched melanoma patients using a computerized data base of 550 melanoma patients treated at this institution. This data base will enable us to integrate and correlate the results of suppressor cell activity with clinical pathological, genetic and other immunological factors. In this way, potential cause and effect relationships, as well as associations relating to the pathogenesis of the disease and the clinical course can be evaluated. The ultimate goal of this investigation is to design an immunomodulatory strategy using drugs or antisera designed to decrease suppressor cell activity and enhance a favorable tumor immune response.